Further experiments on the identification of the insulin releasing factor, which previous evidence suggests is the 18.39 fragment of ACTH-'CLIP', are in progress using peptide fractions separated from extracts of the obese mouse neurointermediate lobe on biogel columns. The total amount of 'CLIP' in the neurointermediate lobe is about 3.7 micrograms in the obese and lean mice respectively. After 6 hours incubation of the neurointermediate lobe with 14C-proline the specific activity of CLIP is approximately 1.8 nCi/micrograms in both lean and obese mice, whereas after 2 hours incubation it is about 0.5 nCi in the obese mouse, whereas there is no 14C incorporation in the lean mouse. Pulse labelling experiments show that after 15 minutes incubation of the neurointermediate lobe with a mixture of 14C-labelled amino acids followed by a 2-hour or 6-hour incubation in the absence of labelled amino acids, 14C was only incorporated in the fraction with M.W. greater than 6,000. There is some cross-reactivity in this fraction with C-terminal ACTH antiserum. Perifusates of the intact pituitary gland and neurointermediate lobes of obese and lean mice rapidly stimulate insulin secretion in the perfused rat pancreas. Preliminary dilution experiments suggest a quantitative difference in the insulin releasing activity from ob/ob and lean mice pituitary gland. Preliminary experiments with pancreatic islet tissue maintained in tissue culture for 48 hours, have shown a marked and rapid response to the pituitary insulin releasing factor.